IFIBIO HOUSSAY   25014
INSTITUTO DE FISIOLOGIA Y BIOFISICA BERNARDO HOUSSAY
Unidad Ejecutora - UE
artículos
Título:
Compulsive social behavior emerges after selective ablation of striatal cholinergic interneurons
Autor/es:
MARTOS, YANINA V.; BRAZ, BARBARA Y.; BECCARIA, JUAN P.; MURER, M. GUSTAVO; BELFORTE, JUAN E.; MARTOS, YANINA V.; BRAZ, BARBARA Y.; BECCARIA, JUAN P.; MURER, M. GUSTAVO; BELFORTE, JUAN E.
Revista:
JOURNAL OF NEUROSCIENCE
Editorial:
SOC NEUROSCIENCE
Referencias:
Año: 2017 vol. 37 p. 2849 - 2858
ISSN:
0270-6474
Resumen:
The mechanisms underlying social dysfunction in neuropsychiatric conditions such as obsessive-compulsive disorder and Tourette syndrome remain uncertain. However, it is known that dysfunctions in basal ganglia, including a reduced number of striatal cholinergic interneurons (SCIN), are involved in their pathophysiology. To explore the role of SCIN in relation to perseverative behaviors, we characterized a new transgenic mouse model in which inducible ablation of SCIN is achieved with high efficiency in a cell-type- and region-specific manner. Mice were subjected to extensive behavioral testing, including assessment of social behaviors, and corticostriatal functional connectivity was evaluated in vivo. Selective SCIN ablation leads to altered social interactions together with exacerbated spontaneously emitted repetitive behaviors. Lesioned mice showed normal motor coordination, balance, and general locomotion. Interestingly, only environmentally driven, but not self-directed, repetitive behaviors were exacerbated in lesioned mice. Remarkably, in mice with SCIN ablation, the normal pattern of social exploration was replayed continuously. The emerging pattern of social interactions is highly predictable and invariant across time. In vivo electrophysiological recordings indicate that SCIN ablation results in an increase of the functional connectivity between different cortical areas and the motor, but not associative, region of the striatum. Our results identify a role of SCIN in suppressing perseverative behaviors, including socially related ones. In sum, SCIN ablation in mice leads to exacerbated ritualistic-like behaviors that affect social performance, providing a link between SCIN dysfunction and the social impairments present in psychiatric disorders.